— Phase 2 Multicenter, International Clinical Study Selected as Spotlight Presentation at 2020 San Antonio Breast Cancer Symposium –
–Enobosarm Demonstrated Clinically Meaningful Clinical Benefit Rates, Overall Response Rates, Median Radiographic Progression-Free Survival and Well Tolerated Safety Profile in Heavily Pretreated Endocrine and Chemotherapy Resistant Metastatic Breast Cancer Cohorts–
–FDA Agrees to Phase 3 Clinical ARTEST Study for the Treatment of Endocrine Resistant ER+/HER2- Advanced Breast Cancer; Study to Commence in 2Q 2021 —
Estrogen receptor (ER) is present in 85% of all breast cancers, and more than 90% of ER+ positive breast cancers also contain the AR which has been demonstrated to be an important therapeutic target in ER+ breast cancer. Enobosarm is an oral drug that selectively targets the AR in breast cancer without having the unwanted virilizing androgen adverse side effects including facial hair, acne, increase in hematocrit, or liver toxicity, while having potential clinical benefits including increasing muscle and physical function as well addressing cancer treatment induced bone loss and fractures. Enobosarm has extensive nonclinical and clinical experience having been evaluated in 25 separate clinical studies with 2,091 enrolled patients, including three Phase 2 clinical studies in advanced breast cancer. There are also at least two enobosarm investigator-initiated Phase 2 clinical studies in advanced breast cancer.
In the first enobosarm Phase 2 clinical study (G200801), enobosarm 9mg oral daily dosing was evaluated in 22 heavily pretreated women who have confirmed AR+/ER+/HER2- metastatic breast cancer and who have developed resistance to estrogen receptor targeted endocrine therapies and chemotherapy. In this first Phase 2 clinical study, enobosarm demonstrated a clinically meaningful six-month clinical benefit rate (complete responses (CR)+partial responses (PR)+ stable disease (SD)) of 35.3% and had a good safety profile with no reports of virilization, increased hematocrit, or liver toxicity.
Today Veru announces the clinical results of the second enobosarm Phase 2 clinical study (G200802) which were presented at the 2020 San Antonio Breast Cancer Symposium. This was an international, Phase 2, open label, parallel design, randomized study to investigate the efficacy and safety of enobosarm 9mg and 18mg oral daily dosing in 136 heavily pretreated women with ER+/HER2- metastatic breast cancer who had breast cancer progression being treated with multiple lines of endocrine therapy and 90% who had also failed chemotherapy. Patients were randomized to receive enobosarm 9mg (n=72) or 18mg (n=64) oral daily dosing. The primary endpoint was clinical benefit rate at 6 months (defined as CR+PR+SD) by RECIST 1.1. Secondary endpoints included objective response rate, best overall response rate (complete responses + partial responses), radiographic progression-free survival (rPFS), and duration of clinical benefit. Median age was 60.8 years (35-83) for 9mg and 62.1 years (42-81) for the 18mg cohort. AR positivity (>10%) was centrally confirmed in 94.0% and 86.5% of the 9mg and 18mg cohorts, respectively.
The Phase 2 primary endpoint demonstrated clinically meaningful clinical benefit rate of 32% and 29% in the 9mg and 18mg daily enobosarm AR+ cohorts, respectively. At the time the study was terminated, the median duration of clinical benefit was not reached (NR) in the 9mg group (range 8.2 months to NR) and 14.1 months (range 11.0 to 16.5) in the 18mg group. Best overall response rates, AR+ patients that had complete or partial responses, were 35.3% and 25.6% for 9mg and 18mg, respectively. The median progression-free survival was 5.6 months (2.9 to >27.5) and 4.2 months (2.8 to 11) in the 9mg and 18mg groups AR+, respectively. Women being treated with 9mg or 18mg of enobosarm also reported significant improvements in quality of life measurements including mobility, anxiety/depression and pain discomfort.
Overall, enobosarm was well tolerated with most of the observed adverse events being grade 1 and 2. Drug related severe adverse events (SAEs) (Grades 3-4) were observed in 6 patients (8.0%) at the 9mg and 10 patients (16.4%) at the 18mg dose. There were no reports of virilization, increased hematocrit, and liver toxicity.
In both Phase 2 clinical studies, enobosarm demonstrated clinically meaningful efficacy and was well tolerated with no unwanted virilization, no increased hematocrit, and no liver toxicity in a combined 150 women heavily pretreated women with ER+/HER2- metastatic breast cancer who have failed estrogen targeted endocrine therapies and chemotherapy. As the 9mg and 18mg had similar efficacy, but the 9mg had slightly better tolerability, the enobosarm 9mg oral daily dose is the recommended dose for the Phase 3 study.
Based upon the efficacy and safety from these clinical studies, the FDA recently agreed to the Company’s Phase 3 registration open label, randomized, ARTEST clinical study to evaluate efficacy and safety of enobosarm 9mg versus an active comparator (exemestane or tamoxifen) for the treatment of ER+/HER2- metastatic breast cancer in approximately 240 patients who have failed a nonsteroidal aromatase inhibitor (anastrozole or letrozole), fulvestrant, and a CDK4/6 inhibitor. The primary endpoint will be radiographic progression-free survival. In the Phase 3 ARTEST study design, the primary endpoint assumptions anticipate, as this is an earlier treatment cohort (2nd line of treatment for metastatic disease and prior to chemotherapy), the median radiographic progression-free survival will be 7 months for enobosarm treatment group and 3.5 months for the active comparator treatment group. As a comparison from the scientific literature, the observed median radiographic progression-free survival for chemotherapy in this treatment setting is approximately 3.1-3.5 months.
“This Phase 2 study confirms that targeting the androgen receptor with enobosarm results in clinical efficacy. Furthermore, enobosarm was well tolerated as evidenced by improvement in quality of life. These results clearly support the further clinical development in a Phase 3 study of enobosarm for the treatment of metastatic endocrine resistant breast cancer. For breast cancer patients, enobosarm represents a novel class of targeted endocrine therapy that alternatively targets the androgen receptor when endocrine therapies targeting the estrogen receptor stop working,” said Dr. Carlo Palmieri, BSc, MB BS, PhD, FRC, Professor of Translational Oncology and Consultant Medical Oncologist,
“We are extremely excited to have exclusively licensed worldwide rights to enobosarm to add to our oncology pipeline. Enobosarm is a large market opportunity as it represents the first new class of targeted endocrine therapy in ER+ advanced breast cancer in decades. Enobosarm targets AR in ER+ HER2- metastatic breast cancer as a potential second line and/or third line oral daily dosing endocrine therapy option in breast cancer patients that have exhausted endocrine therapies targeting ER, but prior to chemotherapy,” said
The Principal Investigator for both Phase 2 studies, including the G200802 study, was Dr.
The authors and affiliations of those included on the study include
About
The Veru breast cancer pipeline includes enobosarm for hormone sensitive metastatic ER+/HER2- metastatic breast cancer and VERU-111 for taxane resistant metastatic triple negative breast cancer. Enobosarm is an oral, first-in-class, new chemical entity, selective androgen receptor agonist that targets the androgen receptor (AR) in AR+/ER+/HER2- metastatic breast cancer without unwanted virilizing side effects. Enobosarm is the first new class of targeting endocrine therapy in advanced breast cancer in decades. In
Veru is also advancing a new drug formulation in its specialty pharmaceutical pipeline addressing unmet medical needs in urology such as the Tadalafil and Finasteride Combination (ENTADFI®) for the administration of tadalafil 5mg and finasteride 5mg combination formulation dosed daily for benign prostatic hyperplasia (BPH). Tadalafil (CIALIS®) is currently approved for treatment of BPH and erectile dysfunction and finasteride is currently approved for treatment of BPH (finasteride 5mg PROSCAR®) and male pattern hair loss (finasteride 1mg PROPECIA®). The co-administration of tadalafil and finasteride has been shown to be more effective for the treatment of BPH than by finasteride alone. The Company expects to submit the NDA for ENTADFI® in early calendar year 2021.
The Company’s Sexual Health Business commercial product is the FC2 Female Condom / FC2 Internal Condom® (“FC2”), an FDA-approved product for the dual protection against unintended pregnancy and the transmission of sexually transmitted infections. The Company’s Female Health Company Division markets and sells FC2 commercially and in the public health sector both in the
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